It is well-known that electrical stimulation of somatic afferent pathways in the pudendal nerve, posterior tibial nerve, or sacral spinal roots can inhibit bladder activity in both humans and animals, and is clinically effective in treating overactive bladder symptoms. Stimulation of the sacral S3 spinal root is currently a FDA approved therapy for the lower urinary tract disorders including bladder overactivity, urgency, frequency, incontinence, and urinary retention. Although the mechanisms underlying neuromodulation are uncertain, this type of therapy has become popular because lower urinary tract dysfunctions in some patients are difficult to manage with medication.
However, sacral and pudendal neuromodulation requires surgery to implant a stimulator (e.g., InterStim®, Medtronic Inc.) and electrodes. Meanwhile, the standard treatment using tibial nerve neuromodulation involves 30 min stimulation once per week for 12 consecutive weeks through a percutaneously inserted needle electrode cephalad to the medial malleolus (Urgent PC® stimulator, Uroplasty Inc.). It requires skilled medical staff to insert the needle electrode close to the nerve during each clinical visit. If the initial 12 week treatment is effective, a maintenance treatment (once every 2-3 weeks) is usually required. Thus, current neuromodulation treatments are effective to suppress bladder overactivity, but they require surgery or repeated clinical visits that are expensive and inconvenient. A non-invasive neuromodulation method to treat overactive bladder could significantly increase the acceptance of neuromodulation treatment by more patients and reduce the high medical cost of the treatment.
Several non-invasive neuromodulation approaches have been investigated previously in an attempt to treat bladder overactivity, including intra-vaginal (Lindstrom S, Fall M, Carlsson C A, Erlandson B E. The neurophysiological basis of bladder inhibition in response to intravaginal electrical stimulation. J Urol 1983; 129: 405-410) or intra-anal (Godec C, Cass A S, Ayala G F. Bladder inhibition with functional electrical stimulation. Urol 1975; 6:663-666) simulation using ring electrodes located on a vaginal/anal plug, dorsal penile/clitoral nerve stimulation using transcutaneous electrical stimulation applied to the penis, or the perigenital/perianal skin area (Tai C, Shen B, Wang J, Chancellor M B, Roppolo J R, de Groat W C: Inhibitory and excitatory perigenital-to-bladder spinal reflexes in the cat. Am J Physiol Renal Physiol 2008; 294:F591-F602; Wheeler J S, Walter J S, Zaszczurynski P J. Bladder inhibition by penile nerve stimulation in spinal cord injury patients. J Urol 1992; 147:100-103; Walter J S, Wheeler J S, Robinson C J, Wurster R D. Inhibiting the hyperreflexic bladder with electrical stimulation in a spinal animal model. Neurourol Urodyn 1993; 12:241-253; and Wang J, Liu H, Shen B, Roppolo J R, de Groat W C, Tai C: Bladder inhibition or excitation by electrical perianal stimulation in a cat model of chronic spinal cord injury. BJU Int 2009; 103:530-536). However, these approaches targeted very inconvenient locations causing discomfort and difficulty in maintaining the electrodes in place for an extended time period.